The Pharmacogenomics of Anti-Platelet Intervention (PAPI) Study: Variation in Platelet Response to Clopidogrel and Aspirin.

Clopidogrel and aspirin are commonly prescribed anti-platelet medications indicated for patients who have experienced, or are at risk for, ischemic cardiovascular events. The Pharmacogenomics of Anti-Platelet Intervention (PAPI) Study was designed to characterize determinants of clopidogrel and dual anti-platelet therapy (DAPT) response in a healthy cohort of Old Order Amish from Lancaster, PA. Following a loading dose, clopidogrel was taken once a day for 7 days.

Severe coronary artery disease: is there a place for percutaneous coronary intervention?

Management of severe coronary artery disease (CAD), defined as multivessel disease with or without significant left main artery disease remains a topic for considerable discussion. Although coronary artery bypass graft (CABG) surgery has been the mainstay of treatment, the steady pace of improvement in percutaneous coronary intervention (PCI) continues to beg the question as to whether PCI can perform as well as CABG for these patients. This short review is intended to place the recently published SYNTAX (Synergy between PCI with Taxus and Cardiac Surgery) trial in perspective, considering the previous major clinical trials in this field and to further consider whether PCI can be used appropriately in the management of patients with advanced CAD.

Bivalirudin and clopidogrel with and without eptifibatide for elective stenting: effects on platelet function, thrombelastographic indexes, and their relation to periprocedural infarction results of the CLEAR PLATELETS-2 (Clopidogrel with Eptifibatide to Arrest the Reactivity of Platelets) study.

Objectives: The primary objective of this study was to compare the effect of therapy with bivalirudin alone versus bivalirudin plus eptifibatide on platelet reactivity measured by turbidometric aggregometry and thrombin-induced platelet-fibrin clot strength (TIP-FCS) measured by thrombelastography in percutaneous coronary intervention (PCI) patients. The secondary aim was to study the relation of platelet aggregation and TIP-FCS to the occurrence of periprocedural infarction.

Background: Bivalirudin is commonly administered alone to clopidogrel naïve (CN) patients and to patients on maintenance clopidogrel therapy (MT) undergoing elective stenting.

The relation of dosing to clopidogrel responsiveness and the incidence of high post-treatment platelet aggregation in patients undergoing coronary stenting.

Objectives: We determined the effect of clopidogrel dosing on the incidence of nonresponsiveness (NR) and high post-treatment platelet aggregation (post-PA).

Background: We have reported NR after a 300-mg loading dose. Limited information is available on the comparative effect of a 600-mg loading dose on the incidence of NR and high post-PA.

Feasibility of off-pump ASD closure using real-time 3-D echocardiography.

Background: If surgeons could "see " through blood and cardiac chamber walls, it would ultimately be unnecessary to open the heart or use cardiopulmonary bypass to perform procedures such as atrial septal defect (ASD) closure or mitral valve repair. Conventional echocardiography generates cross-sectional images that are not satisfactory as the only visualization for surgical procedures, and current 3-Dimensional (3-D) CT and echo systems take several minutes to compose and process a single still frame. Recently, however, the first system for real-time 3-D echocardiography has been developed.

Survival in Acute Myocardial Infarction Induced by Coronary Ligation: Prognostic Relevance of Certain Hemostatic Factors During the Occlusion Phase.

Alterations in various hemostatic factor have been identified as risk factors for survival after acute myocardial infarction (AMI). However, these clinical data are primarily limited to observations made during the postinfarct stage. We assessed the effects of 50 minutes of left anterior descending artery occlusion on several hemostatic factors and analyzed their changes with outcome in 18 Yorkshire swine.

Serial changes of soluble endothelin-1 levels during myocardial ischaemia-reperfusion. Effects of magnesium, diltiazem and a novel MAC-1 inhibitor.

The key role of endothelin-1 (ET-1) has been recognised in patients with ischaemic heart disease. However, the serial changes of ET-1 during both brief and prolonged ischaemia-reperfusion are poorly known. Serial changes of plasma ET-1 were measured during myocardial stunning (MS) and acute myocardial infarction (AMI).

Plasma fibronectin during myocardial ischemia-reperfusion: effects of magnesium, diltiazem, and a novel Mac-1 inhibitor.

The important role of fibronectin (Fn) has been recognized in patients with ischemic heart disease. However, serial changes of Fn during both brief and prolonged ischemia-reperfusion are poorly known. Plasma Fn was measured during acute myocardial infarction (AMI) and myocardial stunning (MS), and in the absence of myocardial injury.

Deployment of a previously embolized, unexpanded, and disarticulated Palmaz-Schatz stent.

Stent embolization is a rare but acknowledged complication of placement of disarticulated (half) Palmaz-Schatz stents. We report a case in which we diagnosed a previously unrecognized, embolized, undeployed half-stent in the distal LAD, causing slow flow, and then deployed the stent where it lay, resulting in improved flow. The literature on treatment of coronary stent embolization and on cutting and preparing half-stents for deployment is discussed.

Effects of intracoronary diltiazem on certain hemostatic parameters during acute myocardial infarction in swine.

Controversy currently exists regarding the use of diltiazem in the treatment of acute myocardial infarction (AMI). due to conflicting results from clinical trials and animal studies. The purpose of this project was to evaluate the changes in the hemostatic profile during AMI following low dose intracoronary diltiazem infusion.

Bolus magnesium infusion in humans is associated with predominantly unfavourable changes in platelet aggregation and certain haemostatic factors.

Unlabelled: The purpose of this study was an attempt to extrapolate favorable observations on the effects of magnesium on platelets and haemostasis from animal models to humans. Intravenous magnesium in the treatment of acute myocardial infarction has been tested in several large clinical trials and remains controversial. The mechanism for the cardioprotective properties of magnesium is unknown.

Short-term low dose intracoronary diltiazem administered at the onset of reperfusion reduces myocardial infarct size.

Background: Currently, controversy exists regarding the use of calcium-channel blockers in the treatment of acute myocardial infarction (AMI), due to apparent conflicting results from clinical trials and animal models. One hypothesis to explain such a discrepancy proposes that the timing and duration of drug administration might influence its cardioprotective effect. Pretreatment with calcium-channel blockers or their administration during coronary artery occlusion is associated with the diminished infarct size in animal models.

Serial changes of the plasma prostanoids during myocardial ischemia-reperfusion in swine. Effects of magnesium, diltiazem, and a novel Mac-1 inhibitor.

The key role of prostanoids has been recognized in patients with ischemic heart disease. However, serial changes of thromboxane and prostacyclin during both brief and prolonged ischemia-reperfusion are poorly known. These plasma prostanoids were measured during myocardial stunning (MS) and acute myocardial infarction (AMI).

Could coenzyme Q10 affect hemostasis by inhibiting platelet vitronectin (CD51/CD61) receptor?

Improved cardiovascular morbidity and mortality have been observed in several clinical studies of dietary supplementation with coenzyme Q10 (CoQ10, ubiquinone). Several mechanisms have been proposed to explain the effects of CoQ10. One attractive theory links ubiquinone with the inhibition of platelets.

Dietary coenzyme Q10 supplementation alters platelet size and inhibits human vitronectin (CD51/CD61) receptor expression.

Improved cardiovascular morbidity and mortality have been observed in several clinical studies of dietary supplementation with coenzyme Q10 (CoQ10, ubiquinone). Several mechanisms have been proposed to explain the effects of CoQ10, but a comprehensive explanation of its cardioprotective properties is still lacking. One attractive theory links ubiquinone with the inhibition of platelets.

Hemostatic changes after early versus late intracoronary magnesium during acute myocardial infarction in swine.

There has been some debate regarding the benefit of magnesium (Mg) in the treatment of acute myocardial infarction (AMI) because of conflicting results from recent clinical trials. Several different hypotheses have been advanced to explain the cardioprotective properties of Mg, including the influence of the timing of Mg administration during AMI. This experiment was designed to assess the effect of intracoronary Mg on certain hemostatic parameters that are known to change during an AMI.

Changes in the haemostatic profile during magnesium deficiency in swine.

Epidemiological studies of populations living in areas of low magnesium (Mg) intake have consistently shown a higher cardiovascular morbidity. Several hypotheses have been advanced to explain the cardioprotective properties of magnesium. Few studies, however, have analysed the relation of magnesium to haemostasis.

Intracoronary magnesium and diltiazem affect to a similar extent certain hemostatic factors during acute myocardial infarction in swine.

The use of calcium antagonists and magnesium (Mg) in the treatment of acute myocardial infarction is controversial. We compared changes in hemostasis during acute myocardial infarction after either low-dose intracoronary Mg or diltiazem infusion in 20 Yorkshire swine undergoing thoracotomy and coronary artery occlusion for 50 min, followed by 3 h of reperfusion. The first group received MgSO4 (250 mg), delivered at the onset of reperfusion, the second group received diltiazem (2.

Serial changes of natural antithrombotics during myocardial ischemia-reperfusion in swine. Effects of magnesium, diltiazem, and a novel Mac-1 inhibitor.

Plasma antithrombin-III (AT-III), protein S, and protein C were measured during myocardial stunning (MS) and acute myocardial infarction (AMI). The effects of magnesium (Mg), diltiazem, and a Mac-1 inhibitor on their plasma levels were elucidated. Forty-nine open-chest swine underwent brief (8 min) or prolonged (50 min) coronary artery occlusion followed by reperfusion.

Mac-1 inhibitor affects certain hemostatic parameters during myocardial stunning in swine.

Myocardial stunning (MS) is a transient contractile dysfunction occurring subsequent to an episode of ischemia followed by reperfusion. NPC 15669 is a leumedin, which inhibits leukocyte adhesion to the endothelium by blocking Mac-1 upregulation. The effect of NPC 15669 supplementation on the hemostasis during MS is unknown.

Hemostatic changes after dietary coenzyme Q10 supplementation in swine.

Improved cardiovascular morbidity and mortality have been observed in several clinical studies of dietary supplementation with coenzyme Q10 (CoQ10). We elucidated the effect of CoQ10 on certain hemostatic parameters that may influence the progression of heart disease. Twelve Yorkshire swine were randomized to receive diet supplementation with either CoQ10 or placebo for 20 days.

Timing of magnesium therapy affects experimental infarct size.

Background: Controversy exists regarding the use of magnesium in the treatment of acute myocardial infarction (AMI) because of apparent conflicting results from clinical trials. One hypothesis to explain the various clinical observations proposes that the timing of magnesium administration significantly influences its therapeutic effect; ie, supraphysiological levels of Mg2+ must be present at the time of reperfusion for magnesium to produce clinical benefit.

Methods And Results: These experiments evaluated the effect of varying the timing of magnesium administration during AMI.